Lung cancer is the most common form of cancer, accounting for 1.35 million of the 10.9 million new cases of cancer per year. It is also the leading cause of death from cancer-associated disease, accounting for 1.18 million of the 6.7 million cancer-related deaths worldwide (NPL 1). Despite recent improvements in systemic therapy, such as chemotherapy and molecular-targeting therapy, the prognosis of patients with advanced-stage lung cancer remains very poor (NPL 2). Lung cancer recurs in 50% of patients after surgery and less than 25% of patients respond to systemic chemotherapy. Accordingly, more effective treatment modalities are urgently required, and immunotherapy represents one promising approach for future lung cancer therapies (NPLs 3-5).
The success of therapeutic cancer vaccines may ultimately rely on the identification of immunogenic antigens that are overexpressed in tumors relative to normal tissues. Effective induction of cytotoxic T lymphocytes (CTLs) by tumor-associated antigen (TAA) has shown promising results (NPLs 6-7). Recently, the development of cDNA microarray technologies, coupled with genome information, has provided comprehensive profiles of the gene expression of malignant cells, which may then be compared with those of normal cells (NPL 8). Gene expression profiling with cDNA microarray technologies constitutes an effective approach for the identification of new TAAs useful for cancer diagnosis and immunotherapy (NPLs 9-12).
Although several candidate TAAs expressed in lung cancer have been published (NPLs 13-14), it is important to identify multiple TAAs overexpressed in a given cancer to develop more effective T cell-mediated cancer immunotherapy (NPL 15).
CDC45L (cell division cycle 45-like) is an essential cellular protein that functions in both the initiation and elongation of DNA replication to ensure that chromosomal DNA is replicated only once per cell cycle (NPLs 16-19). CDC45L is highly conserved among all eukaryotes, and a targeted disruption of this gene causes embryonic lethality in mice (NPL 20). In adult humans, the vast majority of cells has differentiated and ceased cell division, and only a small population of cells is proliferating in some selfrenewing tissues (NPL 21). Thus, while CDC45L is absent in long-term quiescent, terminally differentiated and senescent human cells, it is present throughout the cell cycle of proliferating cancer cells (NPL 18). Accordingly, CDC45L expression is tightly associated with proliferating cell populations, and thus is considered to be a promising candidate for a novel proliferation marker in cancer cell biology (NPLs 18, 22). However, the usefulness of CDC45L as a target for cancer immunotherapy has not yet been fully investigated.